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NASA NTRS2011

Molecular Mechanisms of Circadian Regulation During Spaceflight

Disruption of the regular environmental circadian cues in addition to stringent and demanding operational schedules are two main factors that undoubtedly impact sleep patterns and vigilant performance in the astronaut crews during spaceflight. Most research is focused on the behavioral aspects of the risk of circadian desynchronization, characterized by fatigue and health and performance decrement. A common countermeasure for circadian re-entrainment utilizes blue-green light to entrain the circadian clock and mitigate this risk. However, an effective countermeasure targeting the photoreceptor system requires that the basic circadian molecular machinery remains intact during spaceflight. The molecular clock consists of sets of proteins that perform different functions within the clock machinery: circadian oscillators (genes whose expression levels cycle during the day, keep the pass of cellular time and regulate downstream effector genes), the effector or output genes (those which impact the physiology of the tissue or organism), and the input genes (responsible for sensing the environmental cues that allow circadian entrainment). The main environmental cue is light. As opposed to the known photoreceptors (rods and cones), the non-visual light stimulus is received by a subset of the population of retinal ganglion cells called intrinsically photosensitive retinal ganglion cells (ipRGC) that express melanopsin (opsin 4 -Opn4-) as the photoreceptor. We hypothesize that spaceflight may affect ipRGC and melanopsin expression, which may be a contributing cause of circadian disruption during spaceflight. To answer this question, eyes from albino Balb/cJ mice aboard STS-133 were collected for histological analysis and gene expression profiling of the retina at 1 and 7 days after landing. Both vivarium and AEM (animal enclosure module) mice were used as ground controls. Opn4 expression was analyzed by real time RT/qPCR and retinal sections were stained for Opn4 immunofluorescence. Opn4 was decreased (abrogated in one case) in retinas that concurrently showed higher evidence of oxidative stress. We propose that oxidative stress can lead to a decrease in melanopsin expression, likely via ipRGC loss or impairment, and thus, it can be a contributing factor to circadian disruption during spaceflight. Countermeasures contemplating the use of light should therefore be complemented with melanopsin expression maintenance and/or reduction in oxidative stress.

Zanello, Susana↗
NASA NTRS1985

Phase shifting two coupled circadian pacemakers - Implications for jet lag

Two Van der Pol oscillators with reciprocal linear velocity coupling are utilized to model the response of the human circadian timing system to abrupt displacements of the environmental time cues (zeitgebers). The core temperature rhythm and sleep-wake cycle simulated by the model are examined. The relationship between the masking of circadian rhythms by environmental variables and behavioral and physiological events and the rates of resynchronization is studied. The effects of zeitgeber phase shifts and zeitgeber strength on the resynchronization rates are analyzed. The influence of intrinsic pacemakers periods and coupling strength on resynchronization are investigated. The simulated data reveal that: resynchronization after a time zone shift depends on the magnitude of the shift; the time of day of the shift has little influence on resynchronization; the strength of zeitgebers affects the rate and direction of the resynchronization; the intrinsic pacemaker periods have a significant effect on resynchronization; and increasing the coupling between the oscillators results in an increase in the rate of resynchronization. The model data are compared to transmeridian flight studies data and similar resynchronization patterns are observed.

Gander, P. H.↗
NASA NTRS1986

Resynchronization of circadian sleep-wake and temperature cycles in the squirrel monkey following phase shifts of the environmental light-dark cycle

Circadian rhythms in physiological and behavioral functions gradually resynchronize after phase shifts in environmental time cues. In order to characterize the rate of circadian resynchronization in a diurnal primate model, the temperature, locomotor activity, and polygraphically determined sleep-wake states were monitored in squirrel monkeys before and after 8-h phase shifts of an environmental light-dark cycle of 12 h light and 12 h dark (LD 12:12). For the temperature rhythm, resynchronization took 4 d after phase delay shift and 5 d after phase advance shift; for the rest-activity cycle, resynchronization times were 3 d and 6 d, respectively. The activity acrophase shifted more rapidly than the temperature acrophase early in the post-delay shift interval, but this internal desynchronization between rhythms disappeared during the course of resynchronization. Further study of the early resynchronization process requires emphasis on identifying evoked effects and measuring circadian pacemaker function.

Wexler, D. B.↗
NASA NTRS1977

Transient circadian internal desynchronization after light-dark phase shift in monkeys

In four conscious chair-acclimatized squirrel monkeys (Saimiri sciureus) studied with lights on (600 lx) from 0800 to 2000 hr daily, prominent 24-hr rhythms in feeding, drinking, activity, body temperature, and urinary potassium, sodium, and water excretion were seen. When the monkeys were subjected to 36 hr of darkness followed by 36 hr of light, each variable demonstrated a circadian rhythm which was not passively dependent on the light-dark cycle. After the 24-hr light-dark cycle was abruptly phase-delayed by 8 hr, all the rhythms resynchronized with the new light-dark cycle phase, demonstrating that light-dark cycles are an effective zeitgeber. However, the resynchronization of the rhythms of feeding, drinking, activity, and body temperature was 90% complete within approximately 2 days while the 90% resynchronization of the urinary rhythms took approximately 5 days. These results suggest that the circadian timing system in S. sciureus may consist of several spontaneously oscillating units which can become transiently uncoupled during perturbations of environmental time cues.

Moore-Ede, M. C.↗
NASA NTRS1977

Cortisol-mediated synchronization of circadian rhythm in urinary potassium excretion

Conscious chair-acclimatized squirrel monkeys (Saimiri sciureus) studied with lights on (600 lx) from 0800 to 2000 hr daily (LD 12:12) display a prominent circadian rhythm in renal potassium excretion. The characteristics of this rhythm were reproduced in adrenalectomized monkeys by infusing 5 mg cortisol and 0.001 mg aldosterone, or 5 mg cortisol alone, between 0800 and 0900 kr daily. When the timing of cortisol administration (with or without aldosterone) was phase-delayed by 8 hr, the urinary potassium rhythm resynchronized by 80% of the cortisol phase shift, but only after a transient response lasting 3-4 days. With the same daily dose of adrenal steroids given as a continuous infusion throughout each 24 hr, urinary potassium excretion showed free-running oscillations no longer synchronized to the light-dark cycle. These results indicate that the circadian rhythm of plasma cortisol concentration acts as an internal mediator in the circadian timing system, synchronizing a potentially autonomous oscillation in renal potassium excretion to environmental time cues and to other circadian rhythms within the animal.

Moore-Ede, M. C.↗
NASA NTRSDate not supplied

Abstract: Orion Lighting Workaround for Maintaining Crew Circadian Entrainment

Introduction. Light is the major environmental time cue of our endogenous circadian pacemaker. Suboptimal crew circadian entrainment (CCE) is common and associated with acute and chronic medical symptoms. Additionally, fatigue from suboptimal CCE promotes problematic use of sleep medications. The Orion Cabin Lighting System (OCLS) consists of monochromatic light-emitting diode (LED) lamps. However, light is a powerful suppressor of melatonin and it is a disruptor of CCE if used at incorrect times. A commercial off the shelf (COTS) dynamic lighting system (COTS-DLS) is a potential workaround for maintaining CCE.

Matthew Lindsey↗
NASA NTRS2011

Fused Reality for Enhanced Flight Test Capabilities

The feasibility of using Fused Reality-based simulation technology to enhance flight test capabilities has been investigated. In terms of relevancy to piloted evaluation, there remains no substitute for actual flight tests, even when considering the fidelity and effectiveness of modern ground-based simulators. In addition to real-world cueing (vestibular, visual, aural, environmental, etc.), flight tests provide subtle but key intangibles that cannot be duplicated in a ground-based simulator. There is, however, a cost to be paid for the benefits of flight in terms of budget, mission complexity, and safety, including the need for ground and control-room personnel, additional aircraft, etc. A Fused Reality(tm) (FR) Flight system was developed that allows a virtual environment to be integrated with the test aircraft so that tasks such as aerial refueling, formation flying, or approach and landing can be accomplished without additional aircraft resources or the risk of operating in close proximity to the ground or other aircraft. Furthermore, the dynamic motions of the simulated objects can be directly correlated with the responses of the test aircraft. The FR Flight system will allow real-time observation of, and manual interaction with, the cockpit environment that serves as a frame for the virtual out-the-window scene.

Bachelder, Ed↗
NASA NTRS2011

Fatigue Management in Spaceflight Operations

Sleep loss and fatigue remain an issue for crewmembers working on the International Space Station, and the ground crews who support them. Schedule shifts on the ISS are required for conducting mission operations. These shifts lead to tasks being performed during the biological night, and sleep scheduled during the biological day, for flight crews and the ground teams who support them. Other stressors have been recognized as hindering sleep in space; these include workload, thinking about upcoming tasks, environmental factors, and inadequate day/night cues. It is unknown if and how other factors such as microgravity, carbon dioxide levels, or increased radiation, may also play a part. Efforts are underway to standardize and provide care for crewmembers, ground controllers and other support personnel. Through collaborations between research and operations, evidenced-based clinical practice guidelines are being developed to equip flight surgeons with the tools and processes needed for treating circadian desynchrony (and subsequent sleep loss) caused by jet lag and shift work. The proper implementation of countermeasures such as schedules, lighting protocols, and cognitive behavioral education can hasten phase shifting, enhance sleep and optimize performance. This panel will focus on Fatigue Management in Spaceflight Operations. Speakers will present on research-based recommendations and technologies aimed at mitigating sleep loss, circadian desynchronization and fatigue on-orbit. Gaps in current mitigations and future recommendations will also be discussed.

Whitmire, Alexandra↗
NASA NTRS1992

Visual cues in low-level flight - Implications for pilotage, training, simulation, and enhanced/synthetic vision systems

This paper reviews some of the sources of visual information that are available in the out-the-window scene and describes how these visual cues are important for routine pilotage and training, as well as the development of simulator visual systems and enhanced or synthetic vision systems for aircraft cockpits. It is shown how these visual cues may change or disappear under environmental or sensor conditions, and how the visual scene can be augmented by advanced displays to capitalize on the pilot's excellent ability to extract visual information from the visual scene.

Foyle, David C.↗
NASA NTRS2002

Tactical Versus Strategic Behavior: General Aviation Piloting in Convective Weather Scenarios

We commonly describe environments and behavioral responses to environmental conditions as 'tactical' and 'strategic.' However theoretical research defining relevant environmental characteristics is rare, as are empirical investigations that would inform such theory. This paper discusses General Aviation (GA) pilots' descriptions of tactical/strategic conditions with respect to weather flying, and evaluates their ratings along a tactical/strategic scale in response to real convective weather scenarios experienced during a flight experiment with different weather information cues. Perceived risk was significantly associated with ratings for all experimental conditions. In addition, environmental characteristics were found to be predictive of ratings for Traditional IMC (instrument meteorological conditions), i.e., aural weather information only, and Traditional VMC (visual meteorological conditions), i.e., aural information and an external view. The paper also presents subjects' comments regarding use of Graphical Weather Information Systems (GWISs) to support tactical and strategic weather flying decisions and concludes with implications for the design and use of GWISs.

Latorella, Kara A.↗
NASA NTRS1978

Thermoregulation is impaired in an environment without circadian time cues

Thirteen adult male squirrel monkeys were restrained to a metabolism chair for periods of two or more weeks within an isolation chamber having controlled environmental lighting and ambient temperature. The monkeys were subjected to mild 6-hour cold exposures at all circadian phases of the day. It was found that a prominent circadian rhythm in body temperature, regulated against mild cold exposure, was present in those monkeys synchronized in a 24-hour light-dark cycle. Cold exposures were found to produce decreased core body temperatures when the circadian rhythms were free running or when environmental time indicators were not present. It is concluded that the thermoregulating system depends on the internal synchronization of the circadian time-keeping system.

Fuller, C. A.↗
NASA NTRS1981

Low-visibility visual simulation with real fog

An environmental fog simulation (EFS) attachment was developed to aid in the study of natural low-visibility visual cues and subsequently used to examine the realism effect upon the aircraft simulator visual scene. A review of the basic fog equations indicated that two major factors must be accounted for in the simulation of low visibility - one due to atmospheric attenuation and one due to veiling luminance. These factors are compared systematically by (1) comparing actual measurements to those computed from the fog equations, and (2) comparing runway-visual-range-related visual-scene contrast values with the calculated values. These values are also compared with the simulated equivalent equations and with contrast measurements obtained from a current electronic fog synthesizer to help identify areas in which improvements are needed. These differences in technique, the measured values, the features of both systems, a pilot opinion survey of the EFS fog, and improvements (by combining features of both systems) that are expected to significantly increase the potential as well as flexibility for producing a very high-fidelity low-visibility visual simulation are discussed.

Chase, W. D.↗
NASA NTRS1982

Low-Visibility Visual Simulation with Real Fog

An environmental fog simulation (EFS) attachment was developed to aid in the study of natural low-visibility visual cues and subsequently used to examine the realism effect upon the aircraft simulator visual scene. A review of the basic fog equations indicated that the two major factors must be accounted for in the simulation of low visibility-one due to atmospheric attenuation and one due to veiling luminance. These factors are compared systematically by: comparing actual measurements lo those computed from the Fog equations, and comparing runway-visual-range-related visual-scene contrast values with the calculated values. These values are also compared with the simulated equivalent equations and with contrast measurements obtained from a current electronic fog synthesizer to help identify areas in which improvements are needed. These differences in technique, the measured values, the Features of both systems, a pilot opinion survey of the EFS fog, and improvements (by combining features of both systems) that are expected to significantly increase the potential as well as flexibility for producing a very high-fidelity, low-visibility visual simulation are discussed.

Chase, Wendell D.↗
NASA NTRS1973

Human control capabilities

The capabilities and limitations of man as an element in a closed loop control system under normal environmental conditions are described. Controller characteristics are enumerated, using manual control, quasilinear models, pilot opinion and ratings, compensatory tracking, optimum control models, motion cues, multiple input tracking, multiple loop tracking, transmission delays, and adaptive manual control. Various controls, manipulators, and displays are also considered.

Young, L. R.↗
NASA NTRS1977

Environmental synchronizers of squirrel monkey circadian rhythms

Various temporal signals in the environment were tested to determine if they could synchronize the circadian timing system of the squirrel monkey (Saimiri sciureus). The influence of cycles of light and dark, eating and fasting, water availability and deprivation, warm and cool temperature, sound and quiet, and social interaction and isolation on the drinking and activity rhythms of unrestrained monkeys was examined. In the absence of other time cues, 24-hr cycles of each of these potential synchronizers were applied for up to 3 wk, and the periods of the monkey's circadian rhythms were examined. Only light-dark cycles and cycles of food availability were shown to be entraining agents, since they were effective in determining the period and phase of the rhythmic variables. In the presence of each of the other environmental cycles, the monkey's circadian rhythms exhibited free-running periods which were significantly different from 24 hr with all possible phase relationships between the rhythms and the environmental cycles being examined.

Sulzman, F. M.↗
NASA NTRS2008

Synthetic Vision Displays for Planetary and Lunar Lander Vehicles

Aviation research has demonstrated that Synthetic Vision (SV) technology can substantially enhance situation awareness, reduce pilot workload, improve aviation safety, and promote flight path control precision. SV, and related flight deck technologies are currently being extended for application in planetary exploration vehicles. SV, in particular, holds significant potential for many planetary missions since the SV presentation provides a computer-generated view for the flight crew of the terrain and other significant environmental characteristics independent of the outside visibility conditions, window locations, or vehicle attributes. SV allows unconstrained control of the computer-generated scene lighting, terrain coloring, and virtual camera angles which may provide invaluable visual cues to pilots/astronauts, not available from other vision technologies. In addition, important vehicle state information may be conformally displayed on the view such as forward and down velocities, altitude, and fuel remaining to enhance trajectory control and vehicle system status. The paper accompanies a conference demonstration that introduced a prototype NASA Synthetic Vision system for lunar lander spacecraft. The paper will describe technical challenges and potential solutions to SV applications for the lunar landing mission, including the requirements for high-resolution lunar terrain maps, accurate positioning and orientation, and lunar cockpit display concepts to support projected mission challenges.

Arthur, Jarvis J., III↗
NASA NTRS1997

Gravity, light and plant form

Plants have evolved highly sensitive and selective mechanisms that detect and respond to various aspects of their environment. As a plant develops, it integrates the environmental information perceived by all of its sensory systems and adapts its growth to the prevailing environmental conditions. Light is of critical importance because plants depend on it for energy and, thus, survival. The quantity, quality and direction of light are perceived by several different photosensory systems that together regulate nearly all stages of plant development, presumably in order to maintain photosynthetic efficiency. Gravity provides an almost constant stimulus that is the source of critical spatial information about its surroundings and provides important cues for orientating plant growth. Gravity plays a particularly important role during the early stages of seedling growth by stimulating a negative gravitropic response in the primary shoot that orientates it towards the source of light, and a positive gravitropic response in the primary root that causes it to grow down into the soil, providing support and nutrient acquisition. Gravity also influences plant form during later stages of development through its effect on lateral organs and supporting structures. Thus, the final form of a plant depends on the cumulative effects of light, gravity and other environmental sensory inputs on endogenous developmental programs. This article is focused on developmental interactions modulated by light and gravity.

NASA Discipline Plant Biology↗
NASA NTRS2000

Effects of Gravity on Insect Circadian Rhythmicity

Circadian rhythms - endogenous daily rhythmic fluctuations in virtually all characteristics of life - are generated and coordinated by the circadian timing system (CTS). The CTS is synchronized to the external 24-hour day by time cues such as the light/dark cycle. In an environment without time cues, the length of an animal's day is determined by the period of its internal pacemaker (tau) and the animal is said to be free-running. All life on earth evolved under the solar day; the CTS exists as an adaptation that allows organisms to anticipate and to prepare for rhythmic environmental fluctuations. All life on earth also evolved under the force of earth's gravitational environment. While it is therefore not surprising that changes in the lighting environment affect the CTS, it is surprising that changes in the gravitational environment would do so. However, recent data from one of our laboratories using the brn-3.1 knockout mouse revealed that this model, which lacks the sensory receptor hair cells within the neurovestibular system, does not respond to exposure to a hyperdynamic environment in the same fashion as normal mice. The brn-3.1 mice did not show the expected suppression of circadian rhythmicity shown by control mice exposed to 2G. Exposure to altered ambient force environments affects the amplitude, mean and timing of circadian rhythms in species from unicellular organisms to man. In addition, there is a circadian influence on the homeostatic response to acute 2G acceleration and pulses of 2G can act as a time cue, synchronizing the CTS. This is of significance because maintenance of internal and external temporal coordination is critical for normal physiological and psychological function. Typically, during adaptation to an increased gravitational environment (+G), an initial acute reaction is followed by adaptation and, eventually, a new steady state (14-16), which can take weeks to months to establish. Until the development of space stations, exposure to microgravity was, of necessity, relatively short in duration. In early spaceflight experiments an organism's internal rhythms often expressed periods that were different from each other, even in the presence of a 24.0 hour light-dark cycle, suggesting that the organism was experiencing internal desynchronization (17, 18). In (micro)G, the body temperature rhythm was delayed with respect to other body rhythms and to the light-dark cycle in rhesus macaques (19) and man (20, 21). In the absence of a light-dark cycle, the circadian rhythm of spore formation persisted in Neurospora crassa, however, both the variability and average period of the rhythm increased (22). The beetle Trigonoscelis gigas, exhibited changes in period during and following 11-13 days in (micro)G (23, 24). Resynchronization of the urinary calcium rhythm following a 1800 phase shift of the LID cycle was retarded in rats exposed to (micro)G compared to 1G controls (25). With the development of the Russian Mir Space Station, long-term controlled microgravity exposure became possible. We recorded activity rhythms from black-bodied Tenebrionid beetles, Trigonoscelis gigas, in (micro)G (spaceflight). Each insect was housed individually within an activity monitor (26) and data (activity counts) were collected and stored in five-minute bins. Thirty-two individual activity monitors were housed within each of 2 experimental kits. The beetles within each kit were divided into two groups and the lighting was controlled separately for each group.

Hoban-Higgins, Tana M.↗